Evaluation of amrubicin with a 5 day administration schedule in a mouse model
Noguchi, T.; Ichii, S.; Morisada, S.; Yamaoka, T.; Yanagi, Y.
Gan to Kagaku Ryoho. Cancer and ChemoTherapy 26(9): 1305-1312
1999
ISSN/ISBN: 0385-0684 PMID: 10478184 Document Number: 501811
It was reported that amrubicin hydrochloride (9-aminoanthracycline SM-5887), showed a higher therapeutic activity than doxorubicin against human tumor xenografts implanted into nude mice with a single treatment schedule. In order to find a more effective treatment schedule, the efficacy, toxicity and pharmacokinetic properties with a 5 consecutive day treatment schedule were investigated. The total amount of the maximum tolerated dose and tumor growth inhibiting activity with a 5 day schedule was found to be higher than with a single administration. High levels of amrubicinol, the active metabolite of amrubicin, was detected in the tumor tissue. It was thus assumed that the improved efficacy with the 5-day schedule resulted from the high accumulation of amrubicinol. Bone marrow suppression at the MTD with the 5 day schedule was severer than with a single dose, but recovery was rapid, similar to that following a single dose. In conclusion, it was demonstrated that a 5 day treatment schedule was more effective than a single administration.